We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
- Authors
Wen Liu; Tanasa, Bogdan; Tyurina, Oksana V.; Tian Yuan Zhou; Gassmann, Reto; Wei Ting Liu; Ohgi, Kenneth A.; Benner, Chris; Garcia-Bassets, Ivan; Aggarwal, Aneel K.; Desai, Arshad; Dorrestein, Pieter C.; Glass, Christopher K.; Rosenfeld, Michael G.
- Abstract
While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1–S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.
- Subjects
HISTONES; LYSINE; CHROMOSOMES; CELL cycle regulation; MITOSIS; HELA cells; PHOSPHORYLATION; GENETIC mutation; BINDING sites
- Publication
Nature, 2010, Vol 466, Issue 7305, p508
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature09272